Prostate Case Limited Met

[Haybrant]

59 yo man diagnosed with high risk Pca Gleason 9 w psa 33. PSMA showed large prostatic disease, left internal iliac nodes (2 nodes that are small), and single right iliac bone metastasis about 3cm in size. From stampede I guess RT can be offered to prostate alone given low burden mets. From stomp oriole there is rationale to offer RT to the single met. What to do about the iliac nodes? Offer whole pelvis up front with intention to radiate the Met after? IPSS is 20. Appreciate the help,

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[BobbyHeenan]

You may be limited based upon what insurance lets you do.

I think there are lots of reasonable approaches here and I'd hesitate to be dogmatic.

I think you can treat the pelvic nodes and prostate then do SBRT to the bone lesion. Or just include the bone lesion as part of the target and lump it in the first course (prostate, nodes, bone lesion) in whatever dealers choice fractionation you like.

I would take the gross nodes to at least 60 Gy (2 Gy equivalent) unless there is bowel all over them, then back off some.

 

[TheWallnerus]

59 yo man diagnosed with high risk Pca Gleason 9 w psa 33. PSMA showed large prostatic disease, left internal iliac nodes (2 nodes that are small), and single right iliac bone metastasis about 3cm in size. From stampede I guess RT can be offered to prostate alone given low burden mets. From stomp oriole there is rationale to offer RT to the single met. What to do about the iliac nodes? Offer whole pelvis up front with intention to radiate the Met after? IPSS is 20. Appreciate the help,

Interested to know... was he metastatic w/o the PSMA scan?

I'd do 70/35 to everything (prost, 2 nodes, bone), and an 8 Gy prostate boost. If nothing else, planning it all en masse will be "easier on the planner's brain." I actually *would not* electively nodally irradiate; perhaps that's weird, correct me if I'm wrong. Seems as if in a case like this elective marrow irradiation would be as necessary as elective pelvic nodal irradiation. I'd lean toward 5fx or less for everything w/ a lower IPSS (and I've not 100% disabused myself of the notion that high Gleason prostate can't also be high alpha/beta).

 

[Haybrant]

Interested to know... was he metastatic w/o the PSMA scan?

I'd do 70/35 to everything (prost, 2 nodes, bone), and an 8 Gy prostate boost. If nothing else, planning it all en masse will be "easier on the planner's brain." I actually *would not* electively nodally irradiate; perhaps that's weird, correct me if I'm wrong. Seems as if in a case like this elective marrow irradiation would be as necessary as elective pelvic nodal irradiation. I'd lean toward 5fx or less for everything w/ a lower IPSS (and I've not 100% disabused myself of the notion that high Gleason prostate can't also be high alpha/beta).

He had the iliac sclerotic lesion on CT then on bone scan they called it degenerative change, somewhat surprising for a Gleason 9 with high psa. So PSMA did help this particular radiologist I would say lol

 

[TheWallnerus]

He had the iliac sclerotic lesion on CT then on bone scan they called it degenerative change, somewhat surprising for a Gleason 9 with high psa. So PSMA did help this particular radiologist I would say lol

Just interesting. How many metastatic cases we missed before PSMA, or since I don’t have PSMA, how many metastatic cases I’m missing now. That said, there is still at least a good few percent chance that bone is a false positive; but the downside to adding it in the treatment volume is almost zero. It is said that the incidence of metastatic prostate cancer is on the rise… I wonder how much PSMA is contributing to that.

 

[BobbyHeenan]

Interested to know... was he metastatic w/o the PSMA scan?

I'd do 70/35 to everything (prost, 2 nodes, bone), and an 8 Gy prostate boost. If nothing else, planning it all en masse will be "easier on the planner's brain." I actually *would not* electively nodally irradiate; perhaps that's weird, correct me if I'm wrong. Seems as if in a case like this elective marrow irradiation would be as necessary as elective pelvic nodal irradiation. I'd lean toward 5fx or less for everything w/ a lower IPSS (and I've not 100% disabused myself of the notion that high Gleason prostate can't also be high alpha/beta).

Yes, I too was questioning whether anything elective would help. I think perfectly appropriate to just treat all the gross disease.

Like I said, hard to be dogmatic. I think most rad oncs would at least say to treat it all and not just the prostate...though evicore may not say that.

 

[Palex80]

Just interesting. How many metastatic cases we missed before PSMA, or since I don’t have PSMA, how many metastatic cases I’m missing now.

A lot!

And finally, this may hurt us - Will-Rogers-wise.

1. Many of these patients which we irradiated with radical intent together with long-term ADT will now by M1 (not necessarily oligo) and will never get RT to the prostate.
2. The lack of efficacy of surgery in high-risk patients may become less pronounced, since the urologists will also use PSMA-staging. Filtering out all the N1/M1 patients that always failed immediately after surgery, but seemed to do better with RT+ADT (with the ADT being the important factor here) may allow the urologists to push once again for surgery in those "pure" N0/M0 patients after PSMA-staging.

 

[Palex80]

I would treat whole pelvis electively, boost prostate + nodes and SBRT the bone met.
Additionaly, long term ADT + abiraterone.

 

[TheWallnerus]

Yes, I too was questioning whether anything elective would help. I think perfectly appropriate to just treat all the gross disease.

Like I said, hard to be dogmatic. I think most rad oncs would at least say to treat it all and not just the prostate...though evicore may not say that.

Is evicore denying prostate RT for good performance status limited Mets patients?

To answer my own question I just rechecked their guidelines and 1) they only allow 55/20 IMRT (which strikes me as too low), and 2) only allow the prostate RT if abiraterone is “contraindicated.”

 

[madchemist89]

Depends how aggressive you want to be. Answers can range from no rt --> hypofrac to prostate only --> definitive rt + sbrt with long term adt. I would have a discussion with patient and feel out what his goals are with treatment. His young age may warrant a more aggressive approach but he will likely fail distantly down the road. If you treat definitively, I would include nodes as there is likely microscopic disease there.

 

[jondunn]

Is evicore denying prostate RT for good performance status limited Mets patients?

To answer my own question I just rechecked their guidelines and 1) they only allow 55/20 IMRT (which strikes me as too low), and 2) only allow the prostate RT if abiraterone is “contraindicated.”

55/20 is what stampede did

 

[Palex80]

Is evicore denying prostate RT for good performance status limited Mets patients?

To answer my own question I just rechecked their guidelines and 1) they only allow 55/20 IMRT (which strikes me as too low), and 2) only allow the prostate RT if abiraterone is “contraindicated.”

55/20 is one of the two schedules used in STAMPEDE Arm H

20 x 2.75 Gy or 6 x 6 Gy (once per week) to the prostate only were utilized for M1 patients.

 

[BobbyHeenan]

Is evicore denying prostate RT for good performance status limited Mets patients?

To answer my own question I just rechecked their guidelines and 1) they only allow 55/20 IMRT (which strikes me as too low), and 2) only allow the prostate RT if abiraterone is “contraindicated.”

I won a prolonged appeal on a similar case about a year or so ago. If I'm remembering correctly they initially were sticking to approving only 55/20. They said if solitary bone met asymptomatic I can't treat it basically.

 

[TheWallnerus]

55/20 is what stampede did

Again, it just "feels" like 78/39 is more than 55/20; and the patient has almost severe urinary bother.

I would treat whole pelvis electively, boost prostate + nodes and SBRT the bone met.
Additionaly, long term ADT + abiraterone.

What is the rationale for giving such different BEDs to all the same tumor cells I am being partly facetious.

 

[Palex80]

Again, it just "feels" like 78/39 is more than 55/20; and the patient has almost severe urinary bother.

Of course it's more. It doesn't only feel more. It's just what Stampede did. I often do 18 x 3 Gy instead.

What is the rationale for giving such different BEDs to all the same tumor cells I am being partly facetious.

I didn't say what BED I would give.
My standard approach would be something like
28 x 1.8 Gy whole pelvis with simultaneous SIBs to the nodes, followed by 8 x 3 Gy to the prostate and SBRT of the bone metastasis with 3 x 10 Gy @80% isodose

Occasionaly, we do boost the nodes not as SIB but sequentially after the 28 x 1.8 Gy.
It all depends on how many of them are there and how close they are near the bowel, usually.

 

[jondunn]

RT to the prostate should be thought about in the context of the new data from PEACE

Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design

Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard...

www.thelancet.com

 

[deleted1116990]

59 yo man diagnosed with high risk Pca Gleason 9 w psa 33. PSMA showed large prostatic disease, left internal iliac nodes (2 nodes that are small), and single right iliac bone metastasis about 3cm in size. From stampede I guess RT can be offered to prostate alone given low burden mets. From stomp oriole there is rationale to offer RT to the single met. What to do about the iliac nodes? Offer whole pelvis up front with intention to radiate the Met after? IPSS is 20. Appreciate the help,

60/20 to prostate. Treat Bone met to 60/20 at same time. Whether you want to cover the nodes up to the level of the met with an intermediate dose is up to you.

Alternatively, if you want to be less aggressive about spraying dose everywhere with still achieving a solid PSA reduction, leave the nodes alone, treat prostate to 55/20, SIB the hotspot to 60 keeping OARs cooler closer to 55. SBRT the bone met to 40/5 at the same time.

 

[evilbooyaa]

Lots of reasonable options here.

I would favor 55/20 to prostate as its a STAMPEDE player (and I don't think full aggressive treatment of the prostate is inherently necessary in this space), consider SIBing the gross disease to 60/20, electively treat the LNs, and either simultaneously treat the bone met to 60/20 or SBRT separately depending on proximity to lymph node vessels.

However, I do think on discussion with patient, going for definitive dose to prostate (20, 28, or ~40Fx is dealer's choice) and equivalent dose (as feasible) to LN and bone met not unreasonable.

Or something fancy like 25Fx whole pelvis with SIB to 60 to LN and iliac then cone down to prostate for remaining treatments.

Depends on how much he minds coming in for treatment.

Combine w/ ADT + Abi. **** EviCore's guidelines of not recommending prostate RT in pts receiving Abi - that is driven purely by money.

 

[jondunn]

Combine w/ ADT + Abi. **** EviCore's guidelines of not recommending prostate RT in pts receiving Abi - that is driven purely by money.

is it though? we don't know that RT helps with combi Abi/ADT. in fact, my understanding from the above peace trial is that RT does not help with Abi/ADT? I may be wrong.

 

[evilbooyaa]

is it though? we don't know that RT helps with combi Abi/ADT. in fact, my understanding from the above peace trial is that RT does not help with Abi/ADT? I may be wrong.

?? The link you posted says some proportion of patients got RT and specifically talks about abi vs Docetaxel. Literally says nothing in the results section about RT. Yes Abi seems to help. Great. We knew that. Why is the onus, now that RT has shown benefit, not to wait until an analysis actually says RT doesn't help?

Here is a link from the paper: "As the preplanned number of progression-free survival and overall survival events had not been reached in the study population at the time this paper was written, the efficacy of radiotherapy remains to be analysed (appendix p 16)."

 

[jondunn]

?? The link you posted says some proportion of patients got RT and specifically talks about abi vs Docetaxel. Literally says nothing in the results section about RT. Yes Abi seems to help. Great. We knew that. Why is the onus, now that RT has shown benefit, not to wait until an analysis actually says RT doesn't help?

Here is a link from the paper: "As the preplanned number of progression-free survival and overall survival events had not been reached in the study population at the time this paper was written, the efficacy of radiotherapy remains to be analysed (appendix p 16)."

It was a a 2 x 2 trial.

arm 1: SOC
arm 2:SOC+RT
arm 3 :SOC+ABi
arm 4: SOC+ABI+RT

based on the figures and the HR, it does not appear RT helps, but perhaps this is forthcoming in a different paper.

again, I could be wrong, but clearly you didnt even read the design of the trial if you just think 'some proportion' got RT when it was a major component of the trial design


I think we don't know enough yet based on this paper, so I agree, but this Peace 2x2 trial has been what people have been waiting for since STAMPEDE to see if RT actually helps in addition to Abi, which we know helps.

 

[communitydoc13]

is it though? we don't know that RT helps with combi Abi/ADT. in fact, my understanding from the above peace trial is that RT does not help with Abi/ADT? I may be wrong.

I saw no analysis of XRT efficacy in this trial.

but clearly you didnt even read the design of the trial if you just think 'some proportion' got RT when it was a major component of the trial design

Pretty sure you can read the paper and realize that no data presented is meaningful in terms of efficacy of XRT here. What they say is there is "no interaction with XRT". What this means is that the abi helps patients who both get and don't get XRT to roughly the same relative degree.

Read the paper. Look at the graphs. There is no presentation of XRT efficacy at present. It could be a lot or none at all.

 

[jondunn]

agree, was misunderstanding the HR on figure 3.

weird to publish a 2x2 trial and ignore half the results.

 

[Palex80]

agree, was misunderstanding the HR on figure 3.

weird to publish a 2x2 trial and ignore half the results.

Results probably not mature yet.

 

[jondunn]

Results probably not mature yet.

but i am trying to figure out why they would be any less mature than the two arms that got abi?

 

[Palex80]

but i am trying to figure out why they would be any less mature than the two arms that got abi?

Perhaps the difference in OS attributed to RT plays out later than Abi itself.

 

[jondunn]

yeah but they should at least report it! I don't know how lancet let them get away with that.

 

[evilbooyaa]

It was a a 2 x 2 trial.

arm 1: SOC
arm 2:SOC+RT
arm 3 :SOC+ABi
arm 4: SOC+ABI+RT

based on the figures and the HR, it does not appear RT helps, but perhaps this is forthcoming in a different paper.

again, I could be wrong, but clearly you didnt even read the design of the trial if you just think 'some proportion' got RT when it was a major component of the trial design


I think we don't know enough yet based on this paper, so I agree, but this Peace 2x2 trial has been what people have been waiting for since STAMPEDE to see if RT actually helps in addition to Abi, which we know helps.

They literally state that they cannot make any conclusions about the benefit of radiation in the materials and methods, and here you are trying to make conclusions about the benefits of the M&M. I encourage you to improve your reading comprehension before coming at me hot like the bolded. Literally all we know is that some of these folks got RT. Yes it will work out to half of them, but we don't know which half as they are presented in this paper.

*EDIT* - saw your mea culpa above. Let's move on.

 

[evilbooyaa]

but i am trying to figure out why they would be any less mature than the two arms that got abi?

Sigh, my dude/dudette. You have got to read the paper. And the supplementary Appendix, p16, that I linked before, if you want the answer. Below is what is written on p16 of the supplementary appendix (Bolded my emphasis)

The 2x2 factorial design of PEACE-1 offers the possibility to answer two independent questions based on different hypothesis: the question of Abiraterone efficacy and the question of Radiotherapy efficacy. However, this manuscript solely reports on the abiraterone question as the efficacy and safety data related to the radiotherapy question will only be analyzed once the pre-planned numbers of rPFS and OS events are reached in the low-volume disease population of mCSPC men. Indeed, the 2013 initial protocol planned to analyze the efficacy of abiraterone and radiotherapy simultaneously as the effect of these treatments was assumed to be identical (HRABI=HRRT=0.75). However, late 2018 and early 2019, the HORRAD and STAMPEDE RT trials results were published. Those trials assessed the efficacy of prostate radiotherapy in the same setting than PEACE-1 (patients with de novo metastatic hormone-sensitive prostate cancer treated by ADT alone as SOC). Neither, the HORRAD trial (n=432) nor the STAMPEDE RT trial (n=2061) found evidence of an overall survival (OS) benefit in the overall population (HR: 0·90, 95% CI 0·70–1·14, and HR: 0·92, 95% CI 0·80–1·06; p=0·266, respectively) but raised the possibility that survival might be improved in a subgroup of patients with low metastatic burden (HR: 0·68, 95% CI 0·42–1·10 and HR: 0·68, 95% CI 0·52–0·90; p=0·007, respectively). In light of these results, we chose to amend the protocol (Amendement n°32 cf Appendix - § 5. Amendments to the study design and statistical analysis plan) and revise our primary objective to confirm HORRAD and STAMPEDE RT findings regarding the efficacy of prostate radiotherapy in patients with low metastatic burden. The timing of the analysis is based on the number of events in this subgroup (299 radiographic progressions or deaths for the rPFS analysis and 213 deaths for the OS analysis). So far, these predefined numbers of events have not been reached in the PEACE1 patients with low metastatic burden. We had anticipated this situation in the protocol, which in the chapter “9.3. Interim and final analysis” p51 reads: “It is likely that the analyses of OS for the abiraterone question and the prostate radiotherapy questions will be performed separately due to different onset of deaths in the subgroups of interest (ADT+docetaxel population for abiraterone, that of low metastatic burden population for prostate radiotherapy)” and in the chapter “9.5.2 Analysis of Efficacy endpoints” p52 reads: “If the analysis of prostate radiotherapy and that of abiraterone are not performed at the same time, analysis of abiraterone will be adjusted on radiotherapy but the HRRADIOTHERAPY will not be made public”.
Consequently, the radiotherapy efficacy question will be analyzed and published in due course

 

[jondunn]

Good job!

 

[Chartreuse Wombat]

Sigh, my dude/dudette. You have got to read the paper. And the supplementary Appendix, p16, that I linked before, if you want the answer. Below is what is written on p16 of the supplementary appendix (Bolded my emphasis)

It is always about the # of events

 

[deleted1111261]

Sigh, my dude/dudette. You have got to read the paper. And the supplementary Appendix, p16, that I linked before, if you want the answer. Below is what is written on p16 of the supplementary appendix (Bolded my emphasis)

The rudeness is just such a pain to address - every single day, pretty much every single post - gotta hand it to you @evilbooyaa for being much nicer than you needed to be.

 

[SneakyBooger]

Start ADT for 3-6 months.

Then prostate 7800'ish/180-200. No ENI.

Watch the others. Radiate if/when progress.

Incurable.

QOL = important

 

[jondunn]

Start ADT for 3-6 months.

Then prostate 7800'ish/180-200. No ENI.

Watch the others. Radiate if/when progress.

Incurable.

QOL = important

If quality of life is important - why Give dose escalated RT that doesn’t improve OS even in the curable setting though? And make someone come in daily for 9 weeks?

I agree with 55-60/20 to primary along with ADT/abi, consideration of treating the met now as well, though differnt ways to sequence it that I think are all fair

 

[Palex80]

If quality of life is important - why Give dose escalated RT that doesn’t improve OS even in the curable setting though?

He didn't say whose QOL is important.

 

[SneakyBooger]

If quality of life is important - why Give dose escalated RT that doesn’t improve OS even in the curable setting though? And make someone come in daily for 9 weeks?

I agree with 55-60/20 to primary along with ADT/abi, consideration of treating the met now as well, though differnt ways to sequence it that I think are all fair

From SWOG 1802 Protocol:

 

[SneakyBooger]

He didn't say whose QOL is important.

I see many responses with little (if any) high quality data to support them.

One option I don't see is a single response recommending 6Gy x 6. Yet, according to the STAMPEDE "investigators' opinions" (see below), 6 Gy X 6 is a SOC option and approximately half of all patients in the STAMPEDE Trial received this treatment.

I wonder why no one here would recommend 6GY X 6?

I am certain the absence of that recommendation has nothing to do with 6 fractions in the US not being billed as SBRT. That is ABSOLUTELY not possible. We are above that, are we not. We are just better. Who said nothing under the sun has changed.

Hold on, I have to get that log out of my eye.

STAMPEDE also states: "the optimum dose schedule and technique are uncertain", yet some here somehow do seem to know. I am wondrously humbled and grateful.

As an aside, they also state "It was FELT (74 Gy in 37 fractions) would be too burdensome for patients with metastatic disease." I have had no patients refuse a standard course of radiotherapy after discussing the "investigator's opinions method" used to determine the hypofractionated schemes utilized in STAMPEDE.
XRT in UK is given under an "NHS reimbursement tariff". Perhaps one day there will be a "USA/CMS reimbursement tariff" (APM) in place and rad onc's will have no choice but to deliver radiotherapy that "demonstrates good alignment" with the tariff and is derived from "opinions" rather than high quality data.

Until then, I will discuss with patients a fractionation schedule that has safely been delivered for decades and has 20+ year high quality data to support it.

(Wait just a minute - will BRB - I have to put some hydrogel spacer between a 9 cm lung met that is invading the aorta so I can give it SBRT - it'll be real quick)

From STAMPEDE:

As for the oligomet, STOMP and ORIOLE were in oligoRECURRENT disease, not de novo.

 

[jondunn]

36/6 is great too. ive used it.

 

[SneakyBooger]

36/6 is great too. ive used it.

And nothing under the sun has changed...

 

[deleted1111261]

36/6 didn’t look like it worked as well on that study. I tweeted about it and everyone be like “Simul, grownups talkin here and that wasn’t a variable blah blah blah 36/6 is fine.” One of the folks that justified it said he did it even faster… in 5 fractions. His name may or may not rhyme with Van Cat. That is nice to drop it one fraction. Keep it a clean multiple of 5.

Study doesn’t make me feel happy about it. Look it up, see what you think. If a patient can’t make it in for 4-5.5 weeks or treatment, then why are we treating again? 70/28 , 60/20, 36.25/5 .. 6 weekly fractions? No thank you.

 

[evilbooyaa]

36/6 didn’t look like it worked as well on that study. I tweeted about it and everyone be like “Simul, grownups talkin here and that wasn’t a variable blah blah blah 36/6 is fine.” One of the folks that justified it said he did it even faster… in 5 fractions. His name may or may not rhyme with Van Cat. That is nice to drop it one fraction. Keep it a clean multiple of 5.

Study doesn’t make me feel happy about it. Look it up, see what you think. If a patient can’t make it in for 4-5.5 weeks or treatment, then why are we treating again? 70/28 , 60/20, 36.25/5 .. 6 weekly fractions? No thank you.

Totally altruistic reasons, I'm sure to drop that 6th fraction. Totally could to 7Gy x 5fx with same outcomes though.

 

[DoctwoB]

59 year old man.

Radiate the prostate, nodes and the bone lesion. ADT + abiraterone

 

[seper]

59 year old man.

Radiate the prostate, nodes and the bone lesion. ADT + abiraterone

59 years old man. Save therapies that would kill his QOL for the future

 

[DoctwoB]

59 years old man. Save therapies that would kill his QOL for the future

Until he’s widely metastatic and there is no point? These are precisely the patients where aggressive up front therapy can provide durable disease control and get him 7-10 years with a decent QOL. Limited data from multiple sources in prostate cancer (COMET, series of salvage LNDs, etc) shows treating foci of metastatic disease can provide prolonged periods of disease control. Many RCTs show adding NHT to ADT up front In metastatic disease prolongs all good outcomes.

Good to know that xrt kills your QOL though 😂

 

[CodeRedDew]

Surprised many people actually use 55/20 honestly. To me it’s always seemed a little low esp considering trials like CHHip have demonstrated that non-inferiority could NOT be claimed for 57/19, which is pretty close (actually slightly higher biologically) to 55/20. I get it’s a different patient population but principles of curative-intent dosing to primary site should still apply no?

 

[jondunn]

I get it’s a different patient population but principles of curative-intent dosing to primary site should still apply no?

im not sure that they should.

60/20 MAYBE has better biochemical control than 55/20, maybe, but no other outcome would be improved.

on the other hand, we know that we can do it safely, so i have no issue with it.

 

[jondunn]

36/6 didn’t look like it worked as well on that study. I tweeted about it and everyone be like “Simul, grownups talkin here and that wasn’t a variable blah blah blah 36/6 is fine.” One of the folks that justified it said he did it even faster… in 5 fractions. His name may or may not rhyme with Van Cat. That is nice to drop it one fraction. Keep it a clean multiple of 5.

Study doesn’t make me feel happy about it. Look it up, see what you think. If a patient can’t make it in for 4-5.5 weeks or treatment, then why are we treating again? 70/28 , 60/20, 36.25/5 .. 6 weekly fractions? No thank you.

thanks for the info, I didnt lnow about the difference in the study.

however, I take issue with the bolded comment. The same exact logic could be applied to many other disease sites, including breast or palliation btw. Which I know you have spoken up about that you support shorter courses.

I used it once on a patient where coming weekly worked much better for the patient's needs. coming weekly or 3weekly or 6weekly is a common thing for many of our patients from their systemic therapies, and the idea of coming once a week is much more convenient for some patients.